IMPACT OF ACUTE HYPERGLYCAEMIA ON RESPIRATORY OUTPUT AND PATTERN GENERATION

Obstructive sleep apnoea (OSA) is aetiologically complex. Comorbidity and shared risk factors between OSA and type 1/2 diabetes suggest a potential interaction between hypoxia and/or hypercapnia exposure and hyperglycaemic response. However, the nature of this interaction and likely involvement of hypothalamic and brainstem autonomic/respiratory control sites is not well understood.To model pathophysiological phenotypes of OSA, C57/Bl6 mice (UNSW ACEC, iRECS6615) were exposed to chronic intermittent(1-min on/ 2-min off) hypoxia(10% O₂, n=4), hypercapnia(10% CO₂, 30% O₂, n=4) and hypoxia/hypercapnia(12% O₂, 8% CO₂, n=4) or room air controls (n=4) for 5 hours/day for 7 days.
Subsequently, the animals were isoflurane-anesthetised; external intercostal muscle electromyography (EMG) and electrocardiograph were recorded for a 30-minute baseline and for one-hour after intravenous glucose (0.75 g/kg).
Baseline respiratory rate did not differ between the groups (One-way-ANOVA, p=0.1654). Post-hyperglycaemia respiratory rate reduction (56%), heart rate increase (51%), and heart rate variability reduction (15%) were observed in all groups relative to each baseline. Respiratory rate reduction onset was significantly delayed in the hypercapnia group (One-way-ANOVA, p=0.0391). Comparable EMG amplitude across the groups and timepoints (Mixed-effect analysis, p=0.4534), suggests preserved inspiratory drive despite inspiratory/expiratory ratio change. Respiratory rate reduction was driven by expiratory time prolongation, indicating altered brainstem respiratory pattern generation dynamics. In conclusion, altered autonomic output elicited by acute hyperglycaemia may influence brainstem respiratory pattern generation, which could exacerbate preexisting ventilatory vulnerabilities in OSA.